Key enzymes from the hexose monophosphate shunt, glycolysis and the tricarboxylic acid cycle were compared in lymphoid components of 18 and 24 month old rats. Metabolic alterations that result in critical immunobiochemical lesions may be responsible for the decline in host resistance and increase in autoimmunity common to the aging process. Enzyme analysis in thymus and pulmonary macrophages indicated depression of biosynthetic pathways suggestive of decline of cell-mediated function with age, whereas splenic enzyme activity did not decline with age. The latter interpretation was confounded by the heterogeneity of the spleen cell population but is consistent with unchanged humoral immune function during aging.